Developing multifunctional therapeutic and diagnostic (theranostic) nanoplatforms is critical for addressing challenging issues associated with cancers. Here, self-assembled supernanoparticles consisting of superparamagnetic Fe3O4 nanoparticles and photoluminescent PbS/CdS quantum dots whose emission lies within the second biological window (II-BW) are developed. The proposed self-assembled Fe3O4 and PbS/CdS (II-BW) supernanoparticles [SASNs (II-BW)] exhibit outstanding photoluminescence detectable through a tissue as thick as 14 mm, by overcoming severe light extinction and concomitant autofluorescence in II-BW, and significantly enhanced T2 relaxivity (282 mM–1 s–1, ca. 4 times higher than free Fe3O4 nanoparticles) due to largely enhanced magnetic field inhomogeneity. On the other hand, SASNs (II-BW) possess the dual capacity to act as both magnetothermal and photothermal agents, overcoming the main drawbacks of each type of heating separately. When SASNs (II-BW) are exposed to the dual-mode (magnetothermal and photothermal) heating, the thermal energy transfer efficiency is amplified 7-fold compared with magnetic heating alone. These results, in hand with the excellent photo- and colloidal stability, and negligible cytotoxicity, demonstrate the potential use of SASNs (II-BW) for deep-tissue bimodal (magnetic resonance and photoluminescence) in vivo imaging, while simultaneously providing the possibility of SASNs (II-BW)-mediated amplified dual-mode heating treatment for cancer therapy.

NMR applied to living organisms is arguably the ultimate tool for understanding environmental stress responses and can provide desperately needed information on toxic mechanisms, synergistic effects, sublethal impacts, recovery, and biotransformation of xenobiotics. To perform in vivo NMR spectroscopy, a flow cell system is required to deliver oxygen and food to the organisms while maintaining optimal line shape for NMR spectroscopy. In this tutorial, two such flow cell systems and their constructions are discussed: (a) a single pump high‐volume flow cell design is simple to build and ideal for organisms that do not require feeding (i.e., eggs) and (b) a more advanced low‐volume double pump flow cell design that permits feeding, maintains optimal water height for water suppression, improves locking and shimming, and uses only a small recirculating volume, thus reducing the amount of xenobiotic required for testing. In addition, key experimental aspects including isotopic enrichment, water suppression, and 2D experiments for both 13C enriched and natural abundance organisms are discussed.

Integrating multiple components to realize cancer diagnosis and therapy in a single theranostic nanoplatform has drawn considerable attention. Herein, a multifunctional theranostic nanoplatform (mSiO2@PbS/CdS-Fe3O4) was successfully fabricated by carefully designing thiol-modified large-pore mesoporous silica nanospheres (mSiO2), followed by coordination-driven embedding of Fe3O4 nanoparticles (NPs) and PbS/CdS quantum dots (QDs) inside. The excellent feature of near-infrared (NIR) excitation and NIR emission of PbS/CdS QDs enables deep-tissue photoluminescence imaging, which was demonstrated ex vivo with tissue as thick as 14 mm. Meanwhile, owing to the presence of superparamagnetic Fe3O4 NPs, mSiO2@PbS/CdS-Fe3O4 can be rapidly confined under an external magnetic field (MF), and exhibit a significantly high T 2 relaxivity in T 2-weighted magnetic resonance (MR) images in vivo. When mSiO2@PbS/CdS-Fe3O4 was exposed to external physical stimuli of MF and/or NIR laser, they produced strong local heating through magnetothermal/photothermal effects. Owing to the unique mesoporous structure of mSiO2@PbS/CdS-Fe3O4, doxorubicin (DOX) was readily loaded into them and the drug-release profile was subsequently evaluated under multistimuli (pH/MF/NIR). The release of DOX was significantly enhanced at lower pH, and higher temperatures caused by magnetothermal/photothermal effects. Our results pave the road toward developing a highly powerful nanoplatform for bimodal imaging (NIR deep-tissue photoluminescence and MR imaging), and simultaneously for integrating synergistic treatment capabilities of hyperthermia and pH/MF/NIR-responsive drug release.

Neurovascular coupling (NVC) underlying the local increase in blood flow during neural activity forms the basis of functional brain imaging and is altered in epilepsy. Because astrocytic calcium (Ca) signaling is involved in NVC, this study investigates the role of this pathway in epilepsy. Here, we exploit 4-AP induced epileptic events to show that absolute Ca concentration in cortical astrocyte endfeet in vivo correlates with the diameter of precapillary arterioles during neural activity. We simultaneously monitored free Ca concentration in astrocytic endfeet with the Ca-sensitive indicator OGB-1 and diameter of adjacent arterioles in the somatosensory cortex of adult mice by two-photon fluorescence lifetime measurements following 4-AP injection. Our results reveal that, regardless of the mechanism by which astrocytic endfoot Ca was elevated during epileptic events, increases in Ca associated with vasodilation for each individual ictal event in the focus. In the remote area, increases in Ca correlated with vasoconstriction at the onset of seizure and vasodilation during the later part of the seizure. Furthermore, a slow increase in absolute Ca with time following multiple seizures was observed, which in turn, correlated with a trend of arteriolar constriction both at the epileptic focus and remote areas.

The host evolves redundant mechanisms to preserve physiological processing and homeostasis. These functions range from sensing internal and external threats, creating a memory of the insult and generating reflexes, which aim to resolve inflammation. Impairment in such functioning leads to chronic inflammatory diseases. By interacting through a common language of ligands and receptors, the immune and sensory nervous systems work in concert to accomplish such protective functions. Whilst this bidirectional communication helps to protect from danger, it can contribute to disease pathophysiology. Thus, the somatosensory nervous system is anatomically positioned within primary and secondary lymphoid tissues and mucosa to modulate immunity directly. Upstream of this interplay, neurons detect danger, which prompts the release of neuropeptides initiating (i) defensive reflexes (ranging from withdrawal response to coughing) and (ii) chemotaxis, adhesion and local infiltration of immune cells. The resulting outcome of such neuro‐immune interplay is still ill‐defined, but consensual findings start to emerge and support neuropeptides not only as blockers of TH1‐mediated immunity but also as drivers of TH2 immune responses. However, the modalities detected by nociceptors revealed broader than mechanical pressure and temperature sensing and include signals as various as cytokines and pathogens to immunoglobulins and even microRNAs. Along these lines, we aggregated various dorsal root ganglion sensory neuron expression profiling datasets supporting such wide‐ranging sensing capabilities to help identifying new danger detection modalities of these cells. Thus, revealing unexpected aspects of nociceptor neuron biology might prompt the identification of novel drivers of immunity, means to resolve inflammation and strategies to safeguard homeostasis.

No abstract

The present work aims to provide an accurate description of the tensile behavior of the planar as well as low-buckled stanene and to capture their ideal strength in armchair (AC)-and zigzag (ZZ)-directions. For an accurate description of anisotropic response of such hyperelastic materials as stanene, consideration of a highly nonlinear constitutive model in which up to the fourth power of strains is incorporated is inevitable. By utilizing first principles calculations based on density functional theory (DFT), the second, third, fourth, and fifth order elastic moduli tensors corresponding to both planar and low-buckled states are obtained. Moreover, the morphology of the freestanding stanene such as bond length and lattice parameter is determined; for low-buckled stanene two additional parameters, namely, buckling height and dihedral angle are computed. The effects of uniaxial and biaxial loadings

Our proposed new technique can allow both small and large dye molecules to cross the BRB. While the results are preliminary and thorough evaluation of the retinal tissue following hyperthermia is necessary, this technique has the potential to be an effective mean for the treatment of various diseases such as retinoblastoma.